The present invention relates to a process for preparing an improved carboxymethyl ethyl cellulose.
Carboxymethyl ethyl cellulose (hereinafter referred to as "CMEC") is prepared by reacting carboxymethyl cellulose (hereinafter referred to as "CMC") with an etherifying agent such as an ethyl halide in the presence of a caustic alkali. It is known, as disclosed in U.S. Pat. No. 4,250,305, that when a phase transfer catalyst is employed in the reaction, one of the reaction substrates is solubilized in another phase, that is, the reaction system is made more homogeneous, whereby not only poor reproducibility of ethylation owing to heterogeneous reaction in conventional processes is overcome, but also CMEC of high quality having a uniform distribution of ethoxyl substituent group is obtained.
CMEC has been employed in enteric protective coating. The fundamental physical property required for enteric protective coating films is that the films are not dissolved or disintegrated in gastric juice, but are promptly dissolved in intestinal juice. However, in practical use, only satisfaction of such a requirement is insufficient, and it is required that the shrinkability of films at the time of coating and the mechanical properties of coating films are over specific levels. When the shrinkability of film in film formation is large, even if a uniform coating film is formed, the film is easy to locally cause cracks due to stress that the film receives in gastric juice. Even in the case where no change of film is observed in gastric juice for the sake of appearance, the effect of a medicine is easy to be decreased, since gastric juice penetrates through the cracked portion, thus resulting in fault in practical use. On the other hand, it is also necessary to prevent disintegration of the film owing to external stress at the time of coating or on storage, to say nothing that the film is endurable to stress in gastric juice. From such a point of view, insufficiency in mechanical properties, especially tensile strength and elongation, of the obtained film causes a problem in practical use, since the film is subject to disintegration by external stress.
CMEC has a better hydrolysis resistance than cellulose acetate phthalate used conventionally as an enteric coating material, but still causes change during preparation steps or storage, thus forming a gel material nsoluble in a solvent used for preparing an enteric coating solution, lowering the film-forming property, producing cracks in coating films, or lowering the enteric property (namely requiring a longer time in dissolution). The reason is considered to be that ester linkage such as a lactone is produced by heating under acidic condition.
Coating procedure of CMEC can be conducted in the form of an organic solvent solution, but an aqueous coating liquid is desired from the viewpoint of the economy in process step such as recovery of a solvent and the safety. Dispersion of CMEC into water is carried out by mechanically pulverizing CMEC into fine particles and dispersing the fine particles into water with a plasticizer, dispersing agent, etc. The pulverization of CMEC is industrially disadvantageous in that a large power is required in mechanical pulverization of dried CMEC and moreover the obtained powder is hard to handle owing to dusting.
It is an object of the present invention to provide a process for preparing a depolymerized CMEC excellent in strength of the cast film.
A further object of the invention is to provide a process for preparing a depolymerized CMEC which does not cause chemical and physical changes during the preparation and on storage with the lapse of time.
A still further object of the invention is to provide a process for preparing a depolymerized CMEC which is easy to be dissolved in a solvent and is capable of forming a uniform coating film.
Another object of the invention is to provide a process for preparing a depolymerized CMEC suitable for preparation of an aqueous enteric coating liquid, which has a good dispersibility in water and causes scarcely dusting.
These and other objects of the present invention will become apparent from the description hereinafter.